While it has been demonstrated that Bifidobacteriaceae species are strongly associated with dental caries, there is limited information about cariogenicity of these species. The long-term goal of this research project is to reduce and ultimately help prevent early childhood caries (ECC). The objective of this R21 application is to prove/disprove the concept that Scardovia wiggsiae, which was detected as significantly associated with severe-ECC, is cariogenic in vivo. The central hypothesis is that S. wiggsiae will induce tooth demineralization and produce caries in vivo, acting either acting alone or in synergy with Streptococcus mutans. The rationale for this proposal is that proof of cariogenic potential in vivo would justify in- depth studies of the bacterium's relevance to human dental health, and if so, its cariogenic mechanisms. The central hypothesis and accomplishment of the objective of this application will be tested with the following two specific aims. Aim 1: Cariogenicity of Scardovia wiggsiae in vivo. The working hypothesis is that Scardovia wiggsiae will colonize and induce tooth demineralization in an animal model system. Differing concentrations of the organism will be used to inoculate Sprague Dawley rats fed a cariogenic diet. Animals will be tested for colonization and tissue invasion by S. wiggsiae, and scored for caries. Aim 2: Cariogenicity of Scardovia wiggsiae with S. mutans in vivo. Significant associations between children colonized by both S. wiggsiae and S. mutans and severe-ECC were detected. The working hypothesis is that a combination of S. wiggsiae and S. mutans will colonize and induce more tooth demineralization than either species alone. In Aim 2, the ability for separate infections by S. wiggsiae and S. mutans to induce caries will be compared with a combined S. wiggsiae and S. mutans infection in the same animal model used in Aim 1. Test species colonization and tissue invasion, and dental caries will be assayed. The expected outcomes in Aim 1 will be the demonstration of cariogenicity of a newly named species significantly associated with severe-ECC, and in Aim 2 demonstration of enhanced cariogenicity by the combined infection of S. wiggsiae with S. mutans. The expected confirmation that S. wiggsiae is cario- genic in vivo would have an important positive impact on the field because it would indicate the need for further investigation into the association of the species with diverse populations at risk for caries and determining mechanism(s) of cariogenicity on which to base future improved microbial diagnosis, risk assessment and treatment for early childhood caries. The research proposed is significant because it is expected to enable subsequent definitive studies at the R01 level based on the hypothesis that S. wiggsiae is a caries pathogen in humans. While this proposal stems from species association with severe-ECC, the findings will have direct application for studies of caries in adults including rapidly progressing coronal and root lesions. PUBLIC HEALTH RELEVANCE: The proposed research is relevant to public health because it will prove or disprove the concept that Scardovia wiggsiae is cariogenic. If this species proves to be cariogenic, it would be of public health relevance to test it as a risk indicator for dental caries which would particularly benefit populations with oral health disparities that experience rampant/severe-ECC. The proposed research is relevant to the part of NIH's mission that is described in the priorities of the strategic plan of NIDCR (2009-2013) by integrating a molecular and clinical (in vivo disease model) approach to prove or disprove a diagnostic biomarker for caries risk (Objective I-1), and examining factors that could contribute to oral health inequality (Objective IV-1).